Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water ....Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water and soil should lead to deeper understanding of the dynamics, variation and transfer of genetic material within these resources’ microbial communities, strategies to manage microbial diversity, and improved productivity and long-term sustainability for these resources.Read moreRead less
Reconstructing proteins to explain and engineer biological diversity. The aim of this project is to develop computational methods to construct entirely new proteins. Computational reconstruction of enzymes that have been extinct for over 400 million years has revealed remarkable opportunities for biotechnological innovation. The intended outcomes are to develop bioinformatics methods to broaden the scope of ancestral protein reconstruction to include protein super-families, to establish what spe ....Reconstructing proteins to explain and engineer biological diversity. The aim of this project is to develop computational methods to construct entirely new proteins. Computational reconstruction of enzymes that have been extinct for over 400 million years has revealed remarkable opportunities for biotechnological innovation. The intended outcomes are to develop bioinformatics methods to broaden the scope of ancestral protein reconstruction to include protein super-families, to establish what specific changes led to the evolutionary success of a protein, and to re-run evolution to generate proteins that perform in conditions suitable for industrial and agricultural applications, in particular the production of hydroxylated fatty acids for bioplastics. By examining proteins from many life forms, the project plans to develop a novel bioinformatics strategy to understand their evolution and engineer new proteins for use in production of chemical commodities.Read moreRead less
Computational systems biology: understanding mammalian cell fates using genome-scale network models. Mutations can disrupt the cellular networks that control normal development, causing cells to develop abnormally including in ways that lead to cancer. The project will analyse genome sequences from more than 700 pancreatic cancers and matched controls to precisely map the causative trail from mutations to disrupted networks to altered cell development.
The Stemformatics gene expression compendium: development of multivariate statistical approaches for cross platform analyses. Scientific data is gathered in many different forms, but there are significant gaps in our ability to analyse multiple datasets when generated on different pieces of equipment. This project will study three typical research questions in stem cell biology to develop new analytical approaches to help solve this major data gap.
Using population resequencing data to investigate the evolutionary role and functional impact of inversion polymorphisms. The project will use population re-sequencing data to generate high resolution haplotype maps of inversion polymorphisms in multiple human populations comprising more than 5,000 individuals. These maps will be used to impute inversion polymorphsisms in genotyped samples of more than 100,000 individuals, facilitated by development of novel algorithms for mapping inversion poly ....Using population resequencing data to investigate the evolutionary role and functional impact of inversion polymorphisms. The project will use population re-sequencing data to generate high resolution haplotype maps of inversion polymorphisms in multiple human populations comprising more than 5,000 individuals. These maps will be used to impute inversion polymorphsisms in genotyped samples of more than 100,000 individuals, facilitated by development of novel algorithms for mapping inversion polymorphism from population sequence data. Finally, the project will use this map to assess the functional impact and evolutionary role of inversions, by assessing their effect on quantitative traits and assessing measures of selection and population differentiation. Read moreRead less
Illuminating the microbial world using genome-based fluorescence microscopy. Our understanding of microbial diversity on Earth has been fundamentally changed by metagenomic characterisation of natural ecosystems. Traditional approaches for visualising microbial communities are time-consuming and provide limited information about the identity of specific microorganisms. The proposed research aims to combine single cell genomics and super resolution microscopy for novel, high-throughput, genome-b ....Illuminating the microbial world using genome-based fluorescence microscopy. Our understanding of microbial diversity on Earth has been fundamentally changed by metagenomic characterisation of natural ecosystems. Traditional approaches for visualising microbial communities are time-consuming and provide limited information about the identity of specific microorganisms. The proposed research aims to combine single cell genomics and super resolution microscopy for novel, high-throughput, genome-based techniques to visualise microorganisms, plasmids and viruses, with strain level specificity. The application of these highly scalable approaches will provide comprehensive and unprecedented insight into the fine-scale dynamics and evolution of environmentally and biotechnologically important microbial communities.Read moreRead less
Fine-scale resolution of genomes in natural microbial communities. This project aims to develop advanced molecular and statistical techniques to precisely resolve the genomes of microbes in the environment. Microbes inhabit every niche on the planet and are fundamental to human and animal health, agriculture, and the environment. The proposed technology will advance our understanding of environmental microbes, leading to advances in areas like climate science and biosecurity where microbes play ....Fine-scale resolution of genomes in natural microbial communities. This project aims to develop advanced molecular and statistical techniques to precisely resolve the genomes of microbes in the environment. Microbes inhabit every niche on the planet and are fundamental to human and animal health, agriculture, and the environment. The proposed technology will advance our understanding of environmental microbes, leading to advances in areas like climate science and biosecurity where microbes play a key role. It will also support the development of billion dollar industries focused on the use of beneficial microbes in agriculture, plant, animal, and human health.Read moreRead less
Searching for near-exact protein models. This project aims to develop novel and efficient heuristic-based algorithms leading to near accurate protein tertiary structure models. Knowledge about protein structures is fundamental to our understanding of living systems. The progress on experimental determination of these structures has been extremely limited and remains an open challenge in molecular biology. Computational prediction of protein structures from sequences is emerging as a promising ap ....Searching for near-exact protein models. This project aims to develop novel and efficient heuristic-based algorithms leading to near accurate protein tertiary structure models. Knowledge about protein structures is fundamental to our understanding of living systems. The progress on experimental determination of these structures has been extremely limited and remains an open challenge in molecular biology. Computational prediction of protein structures from sequences is emerging as a promising approach, but its accuracy is far from satisfactory. The software systems developed in this project will be used in structural identification of target proteins in drug design. This will make drug design process more efficient, saving time and cost, potentially saving lives.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.Read moreRead less
Variation in the arginine vasopressin 1a receptor (AVPR1a) gene, the social environment, general health and wellbeing. The project aims to investigate how the arginine vasopressin 1a gene affects gene expression and influences social behaviour and ultimately health and wellbeing. This research will contribute to understanding the importance of individual differences in social policy and interventions aimed at improving health and wellbeing.